Comprehensive evaluation of microRNA as a biomarker for the diagnosis of hepatocellular carcinoma  

作　　者：Juliane Malik Martin Klammer Vinzent Rolny Henry Lik-Yuen Chan Teerha Piratvisuth Tawesak Tanwandee Satawat Thongsawat Wattana Sukeepaisarnjaroen Juan Ignacio Esteban Marta Bes Bruno Kohler Magdalena Swiatek-de Lange 

机构地区：[1]Diagnostics GmbH,Penzberg 82377,Germany [2]Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong 999077,China [3]NKC Institute of Gastroenterology and Hepatology,Songklanagarind Hospital,Hat Yai 90112,Thailand [4]Division of Gastroenterology,Faculty of Medicine,Siriraj Hospital,Mahidol University,Bangkok 10700,Thailand [5]Department of Internal Medicine,Maharaj Nakorn Chiang Mai Hospital,Chiang Mai University,Chiang Mai 50200,Thailand [6]Faculty of Medicine,Srinagarind Hospital,Khon Kaen University,Khon Kaen 40000,Thailand [7]Liver Unit,Vall d’Hebron University Hospital,Barcelona 08035,Spain [8]Transfusion Safety Laboratory,Banc de Sang i Teixits,Barcelona 08005,Spain [9]Department of Medical Oncology,National Center for Tumor Diseases,University Hospital Heidelberg,Heidelberg 69120,Germany [10]Liver Cancer Center Heidelberg,University Hospital Heidelberg,Heidelberg 69120,Germany

出　　处：《World Journal of Gastroenterology》2022年第29期3917-3933,共17页世界胃肠病学杂志（英文版）

摘　　要：BACKGROUND Hepatocellular carcinoma(HCC) is the most common type of primary liver cancer. Current guidelines for HCC management recommend surveillance of high-risk patients every 6 mo using ultrasonography. Serum biomarkers, like alpha-fetoprotein(AFP), protein induced by vitamin K absence/antagonist-Ⅱ(PIVKA-Ⅱ) and lectin-reactive AFP, show suboptimal performance for detection of HCC, which is crucial for successful resection or treatment. Thus, there is a significant need for new biomarkers to aid early diagnosis of HCC. Studies have shown that the expression level of human microRNAs(miRNAs), a small, non-coding RNA species released into the blood, can serve as an early marker for various diseases, including HCC.AIM To evaluate the diagnostic role of miRNAs in HCC as single markers, signatures or in combination with known protein biomarkers.METHODS Our prospective, multicenter, case-control study recruited 660 participants(354 controls with chronic liver disease and 306 participants with HCC) and employed a strategy of initial screening by two independent methods, real-time quantitative PCR(n = 60) and next-generation sequencing(n = 100), to assess a large number of miRNAs. The results from the next-generation sequencing and real-time quantitative PCR screening approaches were then combined to select 26 miRNAs(including two putative novel miRNAs). Those miRNAs were analyzed for their diagnostic potential as single markers or in combination with other miRNAs or established protein biomarkers AFP and PIVKA-Ⅱ via real-time quantitative PCR in training(n = 200) and validation cohorts(n = 300).RESULTS We identified 26 miRNAs that differentiated chronic liver disease controls from(early) HCC via two independent discovery approaches. Three miRNAs, miR-21-5p(miR-21), miR-320a and miR-186-5p, were selected by both methods. In the training cohort, only miR-21, miR-320d and miR-423could significantly distinguish(Q < 0.05) between the HCC and chronic liver disease control groups. In the multivariate setting, miR-21 wi

关 键 词：Carcinoma HEPATOCELLULAR MICRORNAS Biomarkers ALPHA-FETOPROTEIN Protein induced by vitamin K absence-Ⅱ DIAGNOSIS 

分 类 号：R735.7[医药卫生—肿瘤]